Detection of late onset steroid 21-hydroxylase deficiency by capillary gas chromatographic profiling of urinary steroids in children and adolescents

Patients suffering from late onset 21-hydroxylase deficiency (LO-CAH) excreted only slightly higher amounts of 17-hydroxypregnanolone (17-OH-PO), pregnanetriol (PT) and 11-oxo-pregnanetriol (11-O-PT) than age-matched healthy controls. To discriminate between LO-CAH and virilization of unknown origin and precocious pubarche, we calculated the following ratios: (1) pregnanetriol to tetrahydrocortisone (PT/THE), (2) the sum of 17-OH-PO, PT and 11-O-PT (OHP-M) to the sum of THE, tetrahydrocortisol (THF) and allotetrahydrocortisol (a-THF) (C-M) and (3) 11-O-PT to C-M. The following patients were studied: 9 patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency-non-salt losing (CAH-NSL), never treated; 8 patients with CAH (NSL/SL: 3/5) off treatment; 10 patients with LO-CAH; 11 patients with virilization of unknown origin (prepubertal/pubertal: 5/6) and 9 patients with precocious pubarche. Healthy individuals and obligatory heterozygote carriers of comparable ages served as controls. LO-CAH showed increased ratios (median (range)) of PT/THE: 2.27, (1.15–9.09), OHP-M/C-M: 2.30, (1.24–8.15), and 11-O-PT/C-M: 0.24, (0.13–1.23) compared to healthy individuals and heterozygous carriers: PT/THE 0.28, (0.03–0.57), OHP-M/C-M 0.23, (0.06–0.46) and 11-O-PT/C-M<0.01, (<0.01–0.06), respectively. The calculation of ratios, rather than absolute amounts seems to allow the detection of LO-CAH in a single spontaneously voided urine specimen. The clinical and measurable hormonal manifestations of LO-CAH occur at the same time.Abbreviations LO-CAH late onset 21-hydroxylase deficiency - CAH congenital adrenal hyperplasia due to 21-hydroxylase deficiency - SL salt losing - NSL non-salt losing - p.p. prepubertal - p. pubertal - 17-OH-PO 17-hydroxypregnanolone (5-pregnane-3,17-diol-20-one) - PT pregnanetriol (5-pregnane-3,17,20-triol) - 11-O-PT 11-oxo-pregnanetriol (5-pregnane-3,17,20-triol-11-one) - THE tetrahydrocortisone (5-pregnane-3,17,21-triol-11,20-dione) - THF tetrahydrocortisol (5-pregnane-3,11,17,21-tetrol-20-one) - a-THF allotetrahydrocortisol (5-pregnane-3,11,17,21-tetrol-20-one) - OHP-M 17-OH-PO+PT+11-O-PT - C-M THE+THF+a-THFDedicated to Prof. Enno Kleihauer, Ulm, on the occasion of his 60th birthday